Pembrolizumab plus pemetrexed‐platinum significantly improved overall survival (OS) and progression‐free survival (PFS) with manageable safety compared with placebo plus pemetrexed‐platinum in patients with previously untreated metastatic nonsquamous non–small‐cell lung cancer (NSCLC) without EGFR/ALK alterations in the global, randomized, double‐blind, phase 3 KEYNOTE‐189 study. We present results of Japanese patients enrolled in the KEYNOTE‐189 global and Japan extension studies. Patients were randomized 2:1 to intravenous pembrolizumab 200 mg or placebo every 3 weeks (Q3W) for up to 35 cycles. All patients received pemetrexed 500 mg/m2 plus the investigator’s choice of cisplatin or carboplatin Q3W for four cycles, followed by maintenance pemetrexed 500 mg/m2 Q3W (all intravenous). Co–primary endpoints were OS and PFS. Forty Japanese patients enrolled (pembrolizumab, n = 25; placebo, n = 15). At data cutoff (20 May 2019; median time from randomization to data cutoff, 18.5 [range, 14.7‒38.2] months), the median OS was not reached in the pembrolizumab plus pemetrexed‐platinum arm; the median OS was 25.9 (95% confidence interval [CI], 11.9‒29.0) months in the placebo plus pemetrexed‐platinum arm (hazard ratio [HR] .29; 95% CI, .07‒1.15). The median (95% CI) PFS was 16.5 (8.8‒21.1) compared with 7.1 (4.7‒21.4) months (HR, .62; 95% CI, .27‒1.42), respectively. There were no grade 5 adverse events (AE). Grade 3/4 AE occurred in 72% vs 60% of patients in the pembrolizumab vs placebo arms; 40% vs 20% had immune‐mediated AE, and 4% vs 0% had infusion reactions. Efficacy and safety outcomes were similar to those from the global study and support first‐line therapy with pembrolizumab plus pemetrexed‐platinum in Japanese patients with nonsquamous NSCLC without EGFR/ALK alterations.
The usefulness of measuring β2-microglobulin levels in the cerebrospinal fluid (CSF) in neurological diseases is discussed and the relevant literature is reviewed in this article. An elevation of this protein in the CSF is particularly indicative of disease activity in multiple sclerosis, neuro-Behçet’s disease, sarcoidosis, acquired immunodeficiency syndrome-dementia complex and meningeal metastasis of malignant tumors, especially the meningeal dissemination of acute leukemia and malignant lymphoma.
A substantial decline of RVGE hospitalization in 2014 and its persistence was observed among children aged <5 years in Japan after introduction of rotavirus vaccine, although not included in the national immunization program. Indirect effects of rotavirus vaccination were suggested in the 2014 season.
Focal or generalized hemorrhage is a commonly encountered complication in patients with many kinds of amyloidosis. We studied 24 patients (18 males, 6 females) with familial amyloidotic polyneuropathy and found that five had experienced one or more bleeding episodes. In four of these five patients, bleeding occurred in the terminal stage. The incidence of hemorrhage in familial amyloidotic polyneuropathy is lower than that of other types of amyloidosis or that which has been reported in this disease. In our experience clotting abnormalities were rare; clotting factor deficiency appeared not to exist in familial amyloidotic polyneuropathy.
Prealbumin, immunoglobulin G, A, and M concentrations in serum and cerebrospinal fluid from patients with familial amyloid polyneuropathy (Japanese type) were determined and compared with those of asymptomatic relatives or controls. Prealbumin concentrations were not significantly different between them. Using polyacrylamide disc-gel electrophoresis, no qualitative difference in the serum prealbumin was found between them. Among the serum immunoglobulins, only the immunoglobulin A concentration was significantly elevated in the patients as compared with asymptomatic relatives.
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